The overall objectives of this research are: (1) an elucidation of the cellular processes concerned with thyroidal iodide transport, thyroidal hormone synthesis, and thyroidal hormone secretion, and (2) the characterization of the physiological mechanisms which regulate these processes. The experimental approach is through in vitro studies using thyroid cells isolated from trypsin and collagenase dispersed glands. In particular, this research is focused on the intracellular mechanisms through which the regulation of the thyroidal iodide pump is achieved. The findings so far show that the TSH stimulation of this iodide pump is mediated by transcriptional and translational reactions. The RNA and protein products induced in this process are studied by observing their labeling from radioactive nucleotides and amino acids by thyroid cells and by nuclei isolated from the cells. The effects of TSH and of cyclic AMP derivatives added to the cell and nuclei preparations may reveal how TSH acting at receptor sites on the cell surface can bring about activation of nuclear transcription and cytoplasmic translation. Furthermore, observations of he localization of the induced RNA and protein in the cell membranes and organelles may indicate the function of these moieties in the process of stimulation. Another part of this research is the study of the response of the thyroid gland to increases in iodide supply, i.e., the so-called thyroidal autoregulation phenomenon which may serve an important adaptive function. The dispersed thyroid cell system has proven to be a particularly useful in vitro test model for such studies because it responds to added iodide by decreasing iodide pump activity, and, more significantly, by decreasing responsivity to TSH. Evidently these actions of iodide are mediated by an as yet unidentified, iodinated substance, so that the degree of suppression of these cellular functions is in direct proportion to the formation of this substance in the thyroid cells. Present experiments are designed to observe its mode of action.